We examined the relationship of preinjury intelligence, brain tissue volume loss, lesion location, demographic variables and a number of genetic markers to long-term cognitive decline in a group of Vietnam veterans with predominantly penetrating head injury (PHI) suffered more than thirty years ago. Using linear and stepwise regression procedures, we found that those with PHI demonstrated a greater degree of cognitive decline overall during the years following injury compared to a control group of uninjured Vietnam veterans. This became increasingly significant later in life. We also found that preinjury intelligence was the most consistent predictor of cognitive outcome across all phases of potential recovery and decline after such injuries. Laterality of lesion was not a factor. Finally, we found evidence for an association between level of cognitive decline following penetrating head injury and the possession of certain genetic markers that have been linked with brain injury and neurodegeneration. Thus exacerbated decline does occur in Vietnam veterans with PHI, is apparently unrelated to dementia and is determined by multiple factors (most notably preinjury intelligence).